The Role of GRASP55 in Golgi Fragmentation and Entry of Cells into Mitosis

Durán, Juan M.; Kinseth, Matt; Bossard, Carine; Rose, David W.; Polishchuk, Roman; Wu, Christine C.; Yates, John R.; Zimmerman, Timo; Malhotra, Vivek

doi:10.1091/mbc.e07-10-0998

Cited by 82 publications

(91 citation statements)

References 37 publications

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“…An appealing mechanism for intercisternal adhesion has been proposed for the GRASP proteins based on X-ray crystallography and biochemistry that involves PSD-95, Dlg1, Zo-1 domain-dependent homo-oligomerization in trans (13-15). In recent years, with the advent of RNAi-based technologies, knock-down studies have broadly confirmed a role for GRASP proteins and Golgins in controlling Golgi morphology but have not agreed with each other on many notable details, leaving the field in a somewhat confused and conflictory state (10,(15)(16)(17)(18)(19)(20). In the simpler case of Drosophila, dsRNA-mediated depletion of dGRASP results in ∼30% loss of Golgi stacks, whereas double depletion of dGRASP and dGM130 was shown to unstack the Golgi, as examined by EM (21).…”

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confidence: 99%

Membrane adhesion dictates Golgi stacking and cisternal morphology

Lee

Tiwari

Dunlop

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Two classes of proteins that bind to each other and to Golgi membranes have been implicated in the adhesion of Golgi cisternae to each other to form their characteristic stacks: Golgi reassembly and stacking proteins 55 and 65 (GRASP55 and GRASP65) and Golgin of 45 kDa and Golgi matrix protein of 130 kDa. We report here that efficient stacking occurs in the absence of GRASP65/55 when either Golgin is overexpressed, as judged by quantitative electron microscopy. The Golgi stacks in these GRASP-deficient HeLa cells were normal both in morphology and in anterograde cargo transport. This suggests the simple hypothesis that the total amount of adhesive energy gluing cisternae dictates Golgi cisternal stacking, irrespective of which molecules mediate the adhesive process. In support of this hypothesis, we show that adding artificial adhesive energy between cisternae and mitochondria by dimerizing rapamycin-binding domain and FK506-binding protein domains that are attached to cisternal adhesive proteins allows mitochondria to invade the stack and even replace Golgi cisternae within a few hours. These results indicate that although Golgi stacking is a highly complicated process involving a large number of adhesive and regulatory proteins, the overriding principle of a Golgi stack assembly is likely to be quite simple. From this simplified perspective, we propose a model, based on cisternal adhesion and cisternal maturation as the two core principles, illustrating how the most ancient form of Golgi stacking might have occurred using only weak cisternal adhesive processes because of the differential between the rate of influx and outflux of membrane transport through the Golgi.tethers | GRASPs T he Golgi apparatus plays a central role in the processing, sorting, and secretion of various cargo molecules destined for various intracellular and extracellular destinations (1). In animal and plant cells, its unique structure of four to six stacked, roughly planar cisternae serves, among other things, as a platform to organize Golgi resident glycosyltransferases into distinct membrane-bound subcompartments (the cis-, medial-, and trans-Golgi cisternae) for proper and sequential posttranslational maturation of the transiting cargo proteins (2, 3).Although these characteristic features of Golgi morphology have drawn the attention of many researchers for many decades, the molecular mechanisms underlying them are still unclear (4). Pioneering functional reconstitution studies using a cell-free system in which Golgi stacks (but not ribbons) reassemble from mitotic extracts (5-8) yielded two classes of purified proteins, each clearly contributing to stacking: globular Golgi reassembly and stacking proteins (GRASPs; the homologous proteins GRASP65 and GRASP55) (7, 9) and the helical rod-like and partially homologous proteins Golgi matrix protein of 130 kDa (GM130) and Golgin of 45 kDa (Golgin45) (10, 11). One member of each family (GRASP65 and GM130) is located in the cis-most cisterna (7, 12), and another member of each family (GRASP5...

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confidence: 99%

Membrane adhesion dictates Golgi stacking and cisternal morphology

Lee

Tiwari

Dunlop

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…This activity arose as the result of the tethering functions displayed by GRASP65 and GRASP55, through their interactions with their partner proteins GM130 and golgin-45, respectively (2)(3)(4). Several other studies have shown more recently that the GRASPs are involved in the maintenance of the structure of the Golgi ribbon in mammal cells during interphase, in controlling the fragmentation of the Golgi complex at the onset of mitosis (5)(6)(7)(8), in establishing cell polarity in migrating cells (9), and in the consumption of COPII vesicles and the formation of the cis-Golgi in yeast (10).…”

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confidence: 99%

“…Indeed, a direct role for GRASPs in cargo transport has so far been established only for the unconventional secretion routes in Dictyostilium and Drosophila (11,12), whereas they have been shown not to be directly involved in the trafficking of commonly studied reporter cargo proteins along the "conventional" secretory pathway (e.g. the temperature-sensitive (ts-045) mutant of the G protein of vesicular stomatitis virus (VSVG) 2 ) and secretory horseradish peroxidase (5,6,13,14). GRASPs can engage different types of interactions including the ones mediated by their PDZ domains, through which the GRASPs cannot only homodimerize, thus participating in cisternal stacking (15) but can also bind the C-terminal valine motifs (C-TVM) of membrane proteins such as protransforming growth factor ␣ and p24a (16,17).…”

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GRASP65 and GRASP55 Sequentially Promote the Transport of C-terminal Valine-bearing Cargos to and through the Golgi Complex

D’Angelo

Prencipe

Iodice

et al. 2009

Journal of Biological Chemistry

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The Golgi matrix proteins GRASP65 and GRASP55 have recognized roles in maintaining the architecture of the Golgi complex, in mitotic progression and in unconventional protein secretion whereas, surprisingly, they have been shown to be dispensable for the transport of commonly used reporter cargo proteins along the secretory pathway. However, it is becoming increasingly clear that many trafficking machineries operate in a cargo-specific manner, thus we have investigated whether GRASPs may control the trafficking of selected classes of cargo. We have taken into consideration the C-terminal valine-bearing receptors CD8␣ and Frizzled4 that we show bind directly to the PSD95-DlgA-zo-1 (PDZ) domains of GRASP65 and GRASP55. We demonstrate that both GRASPs are needed sequentially for the efficient transport to and through the Golgi complex of these receptors, thus highlighting a novel role for the GRASPs in membrane trafficking. Our results open new perspectives for our understanding of the regulation of surface expression of a class of membrane proteins, and suggests the causal mechanisms of a dominant form of autosomal human familial exudative vitreoretinopathy that arises from the Frizzled4 mutation involving its C-terminal valine.GRASP65 and GRASP55 were identified in in vitro assays as factors that are required for the stacking of the Golgi cisternae (1, 2). This activity arose as the result of the tethering functions displayed by GRASP65 and GRASP55, through their interactions with their partner proteins GM130 and golgin-45, respectively (2-4). Several other studies have shown more recently that the GRASPs are involved in the maintenance of the structure of the Golgi ribbon in mammal cells during interphase, in controlling the fragmentation of the Golgi complex at the onset of mitosis (5-8), in establishing cell polarity in migrating cells (9), and in the consumption of COPII vesicles and the formation of the cis-Golgi in yeast (10).Although the role of the GRASPs in control of the Golgi complex structure (both in interphase and during mitosis) is well established, their involvement in cargo transport along the secretory pathway is still debated. Indeed, a direct role for GRASPs in cargo transport has so far been established only for the unconventional secretion routes in Dictyostilium and Drosophila (11, 12), whereas they have been shown not to be directly involved in the trafficking of commonly studied reporter cargo proteins along the "conventional" secretory pathway (e.g. the temperature-sensitive (ts-045) mutant of the G protein of vesicular stomatitis virus (VSVG) 2 ) and secretory horseradish peroxidase (5, 6, 13, 14). GRASPs can engage different types of interactions including the ones mediated by their PDZ domains, through which the GRASPs cannot only homodimerize, thus participating in cisternal stacking (15) but can also bind the C-terminal valine motifs (C-TVM) of membrane proteins such as protransforming growth factor ␣ and p24a (16,17).Interestingly a C-terminal valine can behave as "transport sign...

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“…24 Phosphorylation of GRASP55 may cause lateral unlinking of stacks, 22 while others could not confirm this observation. 25 Therefore, the molecular mechanisms that organize lateral unlinking remain unclear. However, inhibition of this step prevents cells from entering mitosis, suggesting the activation of a Golgi-specific checkpoint that arrests cells in G 2 .…”

Section: Disassembly Of the Golgi During Mitosismentioning

confidence: 99%

“…However, inhibition of this step prevents cells from entering mitosis, suggesting the activation of a Golgi-specific checkpoint that arrests cells in G 2 . 22,25,26 The observation that the Golgi can still be divided during mitosis even if the cisternae remain stacked, suggests that the potential checkpoint is acting at an early stage when stacks are still intact. 27,28 During prophase and metaphase, the cisternae of the unlinked stacks are then converted into a collection of tubular and vesicular structures by COPI-dependent and COPI-independent mechanisms.…”

Section: Disassembly Of the Golgi During Mitosismentioning

confidence: 99%